ArticleCell2025
Design principles of cell-state-specific enhancers in hematopoiesis.
Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity.Genome biology · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Expression-linked promoter selection (ELiPS) engineers short, strong ubiquitous promoters for gene therapy applications.bioRxiv : the preprint server for biology · 2026Article
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Genome-scale mapping of variant, enhancer and gene function in primary human CD4+ T cells.bioRxiv : the preprint server for biology · 2026Article
- Review
- Review
- Bifunctional transcriptional effector domains control gene expression pulses in an occupancy-dependent manner.bioRxiv : the preprint server for biology · 2025Article
- Motif-based models accurately predict cell type-specific distal regulatory elements.Nature communications · 2025Article
- The specificity landscape of WRKY transcription factors reveals the bidirectional influence of non-CG methylation.Nucleic acids research · 2025Article
- Emergence of activation or repression in transcriptional control under a fixed molecular context.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Trimodal Single-Cell Gene Regulatory Networks Reveal Principles of Stemness Loss and Cell Fate Acquisition in Human Hematopoiesis.bioRxiv : the preprint server for biology · 2025Article
- Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025Review
- Combining Machine Learning and Multiplexed,bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During cellular differentiation, enhancers transform overlapping gradients of transcription factors (TFs) to highly specific gene expression patterns. However, the vast complexity of regulatory DNA impedes the identification of the underlying cis-regulatory rules. Here, we characterized 64,400 fully synthetic DNA sequences to bottom-up dissect design principles of cell-state-specific enhancers in the context of the differentiation of blood stem cells to seven myeloid lineages. Focusing on binding sites for 38 TFs and their pairwise interactions, we found that identical sites displayed both repressive and activating function as a consequence of cell state, site combinatorics, or simply predicted occupancy of a TF on an enhancer. Surprisingly, combinations of activating sites frequently neutralized one another or gained repressive function. These negative synergies convert quantitative imbalances in TF expression into binary activity patterns. We exploit this principle to automatically create enhancers with specificity to user-defined combinations of hematopoietic progenitor cell states from scratch.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.